Efficacy and safety of therapeutic agents can be improved through nano-scale drug delivery systems. Nano-scale drug delivery systems localize drugs in the target tissues in increased amount, increase the drugs stability and permeability across the biological membranes, thus improving their bioavailability and therapeutic efficacy.
Vesicles and micelles based nano drug delivery systems are preferred due to their demonstrated advantages such as unique and diverse structural features, increased drug loading, drugs protection from degradation and ultimately increase in bioavailability of their loaded drugs.
Nano-range vesicular drug carriers are highly biocompatible, biodegradable and are currently getting wider attention amphiphilic nature, biodegradability and ability to carry both hydrophilic and liphophilic drugs. Similarly, their size, shape and lamellarity can be controlled, thus leading to protection of their loaded contents against enzymatic and chemical degradation which in turn improves their therapeutic effects.
Till now, many molecules have been investigated for designing nanocarriers based drug delivery systems. Supramolecular amphiphiles based nano drug delivery systems are preferred due to their multiple versatile properties such as formation of various nano structures upon their spontaneous aggregation. Similarly, upon application of certain stimulus, supramolecular based nano drug delivery systems undergo phase transitions which results in on-demand drug release.
Supramolecular amphiphiles provide a “host-guest” relationship for the hydrophobic drugs by accommodating them in their cavities on molecular levels. This leads to prolonged and sustained release of the guest drugs over a longer time. Macrocycles based supramolecular hosts have got increasing interest for nano drug delivery systems and they have been the precursors for the synthesis of various novel biomedical materials owing to their natural supramolecular self-assembly.
During last three decades, various macrocycles have been synthesized for drug delivery applications. They include crown ethers, catenanes, cyclophanes, cucurbiturils, cryptophanes, calixarenes, porphyrins and carcerands. Nano drug delivery systems based on these macrocycles are able to reduce the drug side effects and improve their pharmacokinetics; yet maximum therapeutic benefits cannot be achieved for the delivered drugs. Thus synthetic scientists are in search of novel supramolecular macrocycles with unique physico-chemical properties for constructing efficient nano drug delivery systems.
The present study reports the synthesis of resorcinarene based a novel amphiphilic supramolecular macrocycle. The synthesis of the amphiphilic supramolecular macrocycle was achieved through two step reaction. In first step, 4-hydroxybenzaldehyde was derivitized with 1-bromohexadecane to get lipophilic intermediate product. In next step, intermediate product was reacted with resorcinol in the presence of acetic acid and sulphuric acid and under the optimized reaction conditions to get amphiphilic supramolecular macrocycle (ASRM) as shown in Scheme 1.
The synthesized amphiphilic supramolecular macrocycle was investigated for its critical micelles concentration (CMC) through UV-visible spectrophotometer.
The synthesized novel amphiphilic supramolecular macrocycle (ASRM) was investigated for its ability of self-assembling in nano-range vesicles in aqueous medium in combination with cholesterol (2:1 ratio w/w).
The drug loading capabilities of the synthesized novel amphiphilic supramolecular macrocycle (ASRM) were explored nano-range vesicles following thin file re-hydration method using Amphotericin B as model hydrophobic drug.
The synthesized amphiphilic supramolecular macrocycle (ASRM) was capable of forming nano-size vesicles upon its self-assembling in aqueous medium and loaded increased concentration of the model hydrophobic drug.